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Protein may beckon the human immunodeficiency virus to active human genes

Summary

Scientists at the Howard Hughes Medical Institute at Columbia University are turning their attention to proteins that might beckon to the correct DNA target within human cells.

The textbook picture of the marauding human immunodeficiency virus (HIV), the virus that causes AIDS, is that it enters the body, commandeers the genetic machinery of human cells and feeds those cells the information they need to mass produce copies of the virus.

That much has been known for years. Yet no one knows how the virus is able to find its way within human cells. Now scientists at the Howard Hughes Medical Institute at Columbia University are turning their attention to proteins that might beckon to the correct DNA target within human cells. For the virus to multiply successfully it must integrate its DNA into human DNA. Only after that step is finished are human cells capable of making the virus.

If a retrovirus is coming into a cell, it makes a lot of sense that it would bind to a protein sitting on DNA being opened up for transcription. After all, it's looking for a likely place to be transcribed.

Stephen P. Goff

HIV integrase is the enzyme that plays a crucial role in seamlessly inserting viral DNA into human DNA so the viral message can be transcribed. Frustrated by a lack of knowledge about how HIV integrase decides to choose one site over another as the site of integration, HHMI investigator Stephen P. Goff decided to look for proteins that might "tell" HIV integrase where to go.

His search netted a protein which he called Ini-1, short for integrase interactor-1. In work reported in the December 23, 1994 issue of Science, Goff and HHMI colleague Gerald R. Crabtree of Stanford University find that Ini-1 looks very much like a component of a yeast gene complex responsible for prying open genes for transcription. The gene complex, called the Snf/Swi ("Sniff/Switch") complex, is under intense scrutiny by Crabtree's laboratory and others because it appears to bind to DNA that is being opened up for transcription.

"If a retrovirus is coming into a cell," Goff said, "it makes a lot of sense that it would bind to a protein sitting on DNA being opened up for transcription. After all, it's looking for a likely place to be transcribed." Goff suggests that HIV integrase sets the stage for viral gene transcription by first searching for and then docking with Ini-1. Goff cautions that this is just a theory right now and more work will be needed to find out if HIV can survive without Ini-1.

"We'd like to learn more about the role of this protein in the life cycle of the virus," Goff said. Questions under consideration include whether Ini-1 controls where the virus goes and whether the protein can be ablated through mutation or drug therapy, thereby possibly snuffing out HIV's beacon.

Scientist Profile

Investigator
Columbia University
Molecular Biology, Virology
Investigator
Stanford University
Genetics, Neuroscience

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